Acute cadmium exposure causes systemic and thromboembolic events in mice

Cadmium (Cd), an environmental and industrial pollutant, poses a potential threat and affects many systems in human and animals. Although several reports on Cd toxicity were presented, the acute effect of Cd on systemic and thrombotic events was not reported so far. Cd (2.284 mg/kg) or saline (control) was injected intraperitoneally (ip), and the systemic parameters were assessed in mice. Compared to control group, acute intraperitoneal injection of Cd, in mice showed significant quickening of platelet aggregation (P<0.001) leading to pial cerebral thrombosis. Likewise, Cd exposure caused a significant increase in white blood cell numbers (P<0.05) indicating the occurrence of systemic inflammation. Also, alanine aminotransferase (ALT) (P<0.05) and creatinine (P<0.01) levels were both significantly increased. Interestingly, the superoxide dismutase activity was significantly decreased in Cd treated group compared to control group (P<0.001), suggesting the occurrence of oxidative stress. We conclude that the Cd exposure in mice causes acute thromboembolic events, oxidative stress and alter liver and kidney functions.     

Trace element distribution in heart tissue sections studied by nuclear microscopy is changed in coxsackie virus B3 myocarditis in methyl mercury-exposed mice

Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3) myocarditis in a direction compatible with the development of chronic disease. Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There are also indications that metals, such as mercury, and trace elements may interact and adversely affect viral replication and development of inflammatory lesions. The effects of low-dose MeHg exposure on myocardial trace element distribution, as determined by means of nuclear microscopy, was studied in CB3 myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12 wk prior to infection. Areas of inflammatory lesions in the myocardium were identified by traditional histologic examination, and serial tissue sections in these selected areas were used for immune histology (macrophages), in situ hybridization of virus genomes, and nuclear microscopy of tissue trace element distribution. Areas with no inflammation or virus were compared with areas of ongoing inflammation and viral replication. In the inflammatory lesions of MeHg-exposed mice as compared to nonexposed mice, the myocardial contents of calcium (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in the inflamed heart may partly explain a more severe disease in MeHg-exposed individuals. Although not significant in the present study, with a limited number of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d 7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section area) in MeHg-exposed mice and, also, there was a tendency of increased persistence of virus with MeHg exposure. No increased MeHg uptake, either in the inflammatory lesions or in the areas of noninflamed heart tissue in infected mice, could be detected. The present results indicate that a "competition" exists between potentially toxic heavy metals from the environment/diet and important trace elements in the body and that a disturbed trace element balance adversely influences the development of pathophysiologic changes in inflammatory heart disease.     

Comparative study of the bioaccumulation and elimination of trace metals (Cd,Pb, Zn,Mn and Fe) in the digestive gland,gills and muscle of bivalve Pinna nobilis during a field transplant experiment

The purpose of this study was to investigate the long-term bioaccumulation and elimination of Cd, Pb, Mn, Zn and Fe by Pinna nobilis tissues after their 90 day-transplantation period at Téboulba fishing harbor. During the transplantation period, the Cd, Pb, Mn, Zn and Fe concentrations in the different tissues of the mussels were measured before and after exposure period. Metal (Cd, Pb, Mn, Zn and Fe) accumulation in P. nobilis mussels varied depending on the analyzed tissue and the caging times. Notable differences in Cd, Pb, Mn, Zn and Fe accumulation patterns within the digestive gland, gills and muscle were found and may be due to the ability of each tissue to accumulate metals. During the depuration phase, the elimination of Cd, Pb, Mn, Zn and Fe depended on the target tissue and the metal speciation. Cd, Pb, Mn and Fe were eliminated rapidly from one organ and increased in other when compared to those of 90 day transplanted mussels. The increase of metal loads during the elimination phase is not clear and particularly what kind of processes is responsible for such response. However, it is reasonable to assume that metals increase is related to the existence of an accumulation/detoxification mechanism, which involves the transport of metals from an organ to another. The data obtained indicate that because of the significantly high quantities of Cd, Pb, Mn, Zn and Fe accumulated during the exposure phase, the transplanted mussels are suitable bioindicators for monitoring trace metals in marine ecosystem.     

Ecological dynamics of emerging bat virus spillover

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.     

Cadmium reduces the efficiency of Sindbis virus replication in human cells and promotes their survival by inhibiting apoptosis

Arthritogenic alphaviruses are emerging arthropod-borne viruses that occasionally cause sporadic to global outbreaks all over the world. Many environmental factors including xenobiotics have been identified as capable of influencing the spread, the susceptibility and the outcome of viral infection. Among them cadmium is a toxic non-essential heavy metal and a prevalent environmental contaminant. In the present study we evaluated the effect of cadmium exposure on alphavirus infection in vitro. We infected Human Embryonic Kidney (HEK) 293 cells in the presence of cadmium chloride (CdCl₂) with Sindbis virus. Cell viability, apoptosis and viral growth were then examined. Our data show that effective doses of cadmium decreased the virus mediated-cell death by inhibition of apoptosis. Moreover, virus growth in HEK 293 cells was also reduced by CdCl₂ treatment. Altogether our results demonstrate that cadmium triggers a protective response which renders HEK 293 cells resistant against Sindbis virus infection.     

Ljungan virus: a commentary on its association with fetal and infant morbidity and mortality in animals and humans

Epidemiologic and experimental data support the notion that Ljungan virus (LV), endemic in some rodent populations in Sweden, Denmark, and the United States, can cause morbidity and mortality in animals and humans. LV infection can cause type I diabetes mellitus, myocarditis, and encephalitis in bank voles and experimental mice, and lemmings. Mouse dams infected with LV experience high rates of stillbirth that may persist across generations, and their fetuses may develop cranial, brain, and limb malformations. In humans, epidemiologic and serologic data suggest that LV infection correlates with intrauterine fetal death, malformations, placental inflammation, myocarditis, encephalitis, and Guillain-Barré syndrome. The proposed role of LV infection in SIDS is unconvincing. Further research is necessary to clarify the role of LV infection in animal and human disease.     

Genetics of life span in mice

Thymic involution that occurs earlier in some individuals than others may be the result of complex interactions between genetic factors and the environment. Such interactions may produce defects of thymus-dependent immune regulation associated with susceptibility to developing autoimmune diseases, malignancy, and an increased number of infections associated with aging.The major histocompatibility complex may be important in determining profiles of cause of death and length of life in mice. Genetic influences on life span involve interactions between loci and allelic interactions during life which may change following viral infections or exposure to other environmental factors. We have used different experimental protocols to study the influence of H-2 on life span and found that interactions between genetic regions, are inconsistent, particularly when comparing mice infected or not infected with Sendai virus.Genes important for life span need to be studied against many genetic backgrounds and under differing environmental conditions because of the complexity of the genetics of life span. Several genetic models were used to demonstrate that the MHC is a marker of life span in backcross and intercross male mice of the H-2^d and H-2^b genotypes in B10 congenic mice. Females lived longer than males in backcross and intercross mice, while males lived longer than females in B10 congenics. H-2^d was at a disadvantage for life span in backcross mice of the dilute brown and brown males exposed to Sendai infection, but intercross mice not exposed to Sendai virus of the same genotype were not at a disadvantage. H-2^d mice were not disadvantaged when compared to H-2^b in B10 congenics that had not been exposed to Sendai virus infection but the reverse was true when they were exposed. Overall, all our studies suggest that genetic influences in life span may involve interactions between loci and many allelic interactions in growing animals or humans. These genetic influences on life span may vary after they are exposed to infections or other environmental conditions. This paper emphasizes the need to use several genetic models, especially animals that have been monitored for infections, to study the genetics of life span.     

Aerosol Exposure to Rift Valley Fever Virus Causes Earlier and More Severe Neuropathology in the Murine Model,which Has Important Implications for Therapeutic Development

Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC) exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirin''s failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential exposure routes and provides important insights into the development and evaluation of potential vaccines and therapeutics to treat RVFV infection.     

Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1) or avian H9N2 (H9N2/G1) virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4⁺ and CD8⁺ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed mice, which might partially be attributed to the immunosuppressive effect of nicotine.     

Induction of reactivation of herpes simplex virus in murine sensory ganglia in vivo by cadmium.

Herpes simplex viruses maintained in a latent state in sensory neurons in mice do not reactivate spontaneously, and therefore the factors or procedures which cause the virus to reactivate serve as a clue to the mechanisms by which the virus is maintained in a latent state. We report that cadmium sulfate induces latent virus to reactivate in 75 to 100% of mice tested. The following specific findings are reported. (i) The highest frequency of induction was observed after two to four daily administrations of 100 micrograms of cadmium sulfate. (ii) Zinc, copper, manganese, or nickel sulfate administered in equimolar amounts under the same regimen did not induce viral reactivation; however, zinc sulfate in molar ratios 25-fold greater than those of cadmium induced viral replication in 2 of 16 ganglia tested. (iii) Administration of zinc, nickel, or manganese prior to the cadmium sulfate reduced the incidence of ganglia containing infectious virus. (iv) Administration of cadmium daily during the first week after infection and at 2-day intervals to 13 days after infection resulted in the recovery from ganglia of infectious virus in titers 10- to 100-fold higher than those obtained from animals given saline. Moreover, infectious virus was recovered as late as 11 days after infection compared with 6 days in mice administered saline. (v) Administration of cadmium immediately after infection or repeatedly after establishment of latency did not exhaust the latent virus harbored by sensory neurons, inasmuch as the fraction of ganglia of mice administered cadmium and yielding infectious virus was similar to that observed in mice treated with saline. We conclude that induction of cadmium tolerance precludes reactivation of latent virus. If the induction of metallothionein genes was the sole factor required to cause reactivation of latent virus, it would have been expected that all metals which induce metallothioneins would also induce reactivation, which was not observed. The results therefore raise the possibility that in addition to inducing the metallothionein genes, cadmium inactivates the factors which maintain the virus in latent state.     

Increased mortality associated with TCDD exposure in mice infected with influenza A virus is not due to severity of lung injury or alterations in Clara cell protein content

Most studies examining the cause of increased mortality in mice infected with a normally non-lethal dose of influenza A virus after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have focused on defects in the immune system. This study examined other possible consequences of TCDD exposure, which could alter pulmonary inflammation during infection. We measured bronchoalveolar lavage (BAL) fluid lactate dehydrogenase (LDH) and protein concentrations and lung wet to dry weight ratios to assess lung damage and edema formation. Immunohistochemistry for Cyp1A1 was used to evaluate the responsiveness of the lung to TCDD. Additionally, we characterized the effects of TCDD on Clara cell secretory protein (CCSP), which plays a regulatory role in pulmonary inflammation. There were no differences in BAL fluid LDH and protein levels, lung wet to dry weight ratios, or the amount of CCSP in the lungs from mice treated with TCDD or vehicle control. The amount of Cyp1A1 in endothelial cells, Clara cells, and Type II pneumocytes was greatly induced after TCDD exposure. Although lung tissue was clearly responsive to TCDD as shown by Cyp1A1 induction, the increased mortality in infected mice exposed to TCDD did not correlate with increased damage to the lung or decreased CCSP concentrations.     

Resistance to Pseudorabies Virus with Enhanced Interferon Production and Natural Killer Cell Activity in Mice Treated with Serum Thymic Factor

Susceptibility to pseudorabies virus (PRV) infection in mice, which were continuously depleted of natural killer (NK) cell activity by injection of anti-asialo GM1, was examined. Effects of serum thymic factor (FTS) on susceptibility of mice to PRV were also investigated. In mice with depleted NK cell activity, the mortality of PRV-infected mice was markedly high, whereas that of FTS-pretreated mice was significantly lower than the controls. Reduced susceptibility to PRV was demonstrated in mice treated with anti-asialo GM1 antisera before the PRV infection. Such a reduced susceptibility was not observed in mice inoculated with the antisera on day 1 post-infection (PI). To analyze the FTS-induced resistance to PRV infection, NK cell activity, macrophage activity, and interferon (IFN) productions were studied. Interferon production and NK cell activity were enhanced in the FTS-pretreated mice, suggesting that interferon may play an important role in this FTS-induced resistance to PRV infection.     

树鼩实验感染基孔肯雅病毒的研究

选用3株基孔肯雅病毒人工感染成年树鼩,进行了病毒血症、抗体动态变化、内脏组织病理改变和病毒在宿主体内定位的研究。结果表明,感染树鼩能产生2～6天的病毒血症。血凝抑制(Hi)抗体第6天产生,第30～50天达高峰:中和(NT)抗体在第10天产生,第30～40天达高峰,二者相关性非常显著(P<0.01)。补体结合(CF)抗体第14天产生,第40～50天为高峰,以后逐渐下降。第8～12天能在其脑、肺、肝、脾和肾等组织查到病毒,经病理检查这些内脏组织呈炎性改变和出血倾向,表明该病毒能侵袭树鼩各主要脏器。试验认为树鼩对基孔肯雅病毒敏感。     

6种重金属对赤子爱胜蚓的急性毒性效应与风险评价

【背景】近年来,土壤重金属污染问题日益凸显,对生态环境、食品安全和人体健康构成了严重威胁,其急性毒性尚未明确。【方法】采用滤纸接触法和人工土壤法测定了铜(Cu2+)、锌(Zn2+)、镍(Ni+)、镉(Cd2+)、铅(Pb2+)和锰(Mn2+)等6种重金属对赤子爱胜蚓的急性毒性效应,并参照欧盟指令91/414/EEC标准评价了其环境风险。【结果】滤纸接触法48h测定结果表明,6种重金属对蚯蚓的LC50为3.17(2.53～3.81)～90.42(69.45～140.47)μg.cm-2,其毒性次序为Cu2+>Zn2+>Ni+>Cd2+>Pb2+>Mn2+。人工土壤法14d测定结果表明,6种重金属对蚯蚓的LC50为1347(1236～1453)～6936(6144～8930)mg.kg-1,其毒性次序为Cu2+>Cd2+>Ni+>Zn2+>Mn2+>Pb2+。风险评价结果显示,Cu2+、Zn2+、Ni+、Cd2+、Pb2+和Mn2+等6种重金属的暴露比(toxicity/exposureratio,TER)分别为3.37、4.46、8.68、1428、13.87和5.85。【结论与意义】6种重金属对土壤动物蚯蚓均具有潜在的毒性效应。Cu2+、Zn2+、Ni+、Mn2+等4种重金属对赤子爱胜蚓存在急性毒性风险,而Cd2+和Pb2+对赤子爱胜蚓的急性毒性风险水平是可接受的。该评价结果可为我国制定基于风险的土壤环境质量标准提供依据。     

Role of Nrf2 in host defense against influenza virus in cigarette smoke-exposed mice

Influenza virus is a common respiratory tract viral infection. Although influenza can be fatal in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, its pathogenesis is not fully understood. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. In the present study, we investigated the role of Nrf2 in protection against influenza virus-induced pulmonary inflammation after cigarette smoke exposure with both in vitro and in vivo approaches. For in vitro analyses, peritoneal macrophages isolated from wild-type and Nrf2-deficient mice were treated with poly(I:C) and/or cigarette smoke extract. For in vivo analysis, these mice were infected with influenza A virus with or without exposure to cigarette smoke. In Nrf2-deficient macrophages, NF-κB activation and the induction of its target inflammatory genes were enhanced after costimulation with cigarette smoke extract and poly(I:C) compared with wild-type macrophages. The induction of antioxidant genes was observed for the lungs of wild-type mice but not those of Nrf2-deficient mice after cigarette smoke exposure. Cigarette smoke-exposed Nrf2-deficient mice showed higher rates of mortality than did wild-type mice after influenza virus infection, with enhanced peribronchial inflammation, lung permeability damage, and mucus hypersecretion. Lung oxidant levels and NF-κB-mediated inflammatory gene expression in the lungs were also enhanced in Nrf2-deficient mice. Our data indicate that the antioxidant pathway controlled by Nrf2 is pivotal for protection against the development of influenza virus-induced pulmonary inflammation and injury under oxidative conditions.     

H5N1禽流感病毒感染小鼠和两种灵长类动物的肺组织病理学比较

目的比较H5N1禽流感病毒感染小鼠、恒河猴及食蟹猴急性期肺组织的病理学变化。方法在麻醉状态下对BALB／c小鼠、恒河猴及食蟹猴进行H5N1病毒滴鼻接种,在感染急性期实施安死术,取肺组织运用H＆E结合免疫组化技术分析肺组织的病理变化。结果BALB／c小鼠感染急性期,肺组织以变质性炎为主,肺泡结构被广泛破坏,以单核细胞为主的炎细胞浸润,局部可见渗出性炎。而在恒河猴感染急性期肺组织病理改变以渗出性炎为主,同时可见变质性炎和增生性炎。在食蟹猴感染急性期肺组织病理改变以渗出性和变质性炎为主,同时亦可见上皮的新生。结论H5N1禽流感病毒感染小鼠与恒河猴、食蟹猴急性期肺组织的病理变化不同,这将为进一步认识禽流感的发病机制及研究针对性的治疗方法提供一些理论依据。     

Midgut and salivary gland barriers to La Crosse virus dissemination in mosquitoes of the Aedes triseriatus group

Vector competence for La Crosse virus (LACV) was compared for four species in the Aedes (Protomacleaya) triseriatus group: Ae. triseriatus (Say), Ae. hendersoni Cockerell, Ae. zoosophus Dyar and Knab and Ae. brelandi Zavortink (Diptera: Culicidae). Rates of replication and dissemination of virus in the mosquito hosts were compared and rates of oral transmission of virus to suckling mice were determined. Barriers to virus dissemination which limited the ability of each species to transmit virus were identified. Ae. zoosophus displayed the highest vector competence for LACV. Both infection and transmission rates were high: 99% and 85% respectively; no significant barriers to LACV were found. Disseminated infection of Ae. triseriatus with LACV was controlled primarily be a midgut escape barrier. When virus was introduced directly into the haemocoel, transmission rates were significantly increased (37% v. 79%). Ae. hendersoni showed high susceptibility to LACV infection but a very low rate of oral transmission (7%). Ae. brelandi was also highly susceptible to infection by LACV and transmitted virus at an intermediate rate (27%). Modulation of vector competence in both Ae. hendersoni and Ae. brelandi resulted from a salivary gland escape barrier. As these four species of mosquitoes comprise a closely related monophyletic series, their differences of vector competence for LACV provide an excellent model for studying the genetic basis of the barriers involved.     

Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis

The neuropathogenesis of influenza-associated encephalopathy in children and Reye's syndrome remains unclear. A surveillance effort conducted during 2000-2003 in South-West Japan reveals that almost all fatal and handicapped influenza-associated encephalopathy patients exhibit a disorder of mitochondrial β-oxidation with elevated serum acylcarnitine ratios (C_16:0+C_18:1)/C₂. Here we show invasion by a non-neurotropic epidemic influenza A H3N2 virus in cerebral capillaries with progressive brain edema after intranasal infection of mice having impaired mitochondrial β-oxidation congenitally or posteriorly in the newborn/ suckling periods. Mice genetically lacking of carnitine transporter OCTN2, resulting in carnitine deficiency and impaired β-oxidation, exhibited significant higher virus-genome numbers in the brain, accumulation of virus antigen exclusively in the cerebral capillaries and increased brain vascular permeability compared to in wild type mice. Mini-plasmin, which proteolytically potentiates influenza virus multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries of OCTN2-deficient mice but only a little in wild-type mice. These results suggest that the impaired mitochondrial β-oxidation changes the susceptibility to a non-neurotropic influenza A virus as to multiplication in the brain capillaries and to cause brain edema. These pathological findings in the brain of mice having impaired mitochondrial β-oxidation after influenza virus infection may have implications for human influenza-associated encephalopathy.     

Study on the aerosol transmission of Hantaan virus

We studied some important aspects constituting aerosol transmission of Hantaan virus, including the possibility of viral aerosol generated by rodents, airborne stability, rodent’s susceptibility to aerosol challenge, and field air sampling for the virus. Our results showed that Hantaan virus aerosol could be generated through the activities of infected mice, and cause specific infection among the exposed animals. Several kinds of rodents such asApodemus agrarius, weaning mice and suckling mice were found to be rather sensitive to the aerosol challenge of Hantaan virus. The 50% of inhaled lethal dose (LD₅₀) of suckling mice is 0.73 (1.4–0.37) plaque-forming unit (pfu). Hantaan virus aerosol was relatively stable in the air at 18–20°C and 70–90% relative humidity. The biological decay rate of the viral aerosol was 4.1% per min during 90 min. We also successfully sampled and isolated Hantaan virus from the working field atmosphere. The data obtained in the study provided more solid evidence for Hantaan virus aerosol transmission among rodents and from rodents to human-beings.     

Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses

Aims: To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. Methods and Results: After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0·05). The YAC‐1 cell‐killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0·01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)‐1β, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)‐1 (P < 0·01). Conclusions: These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell‐mediated immune responses following up‐regulation of lung natural killer (NK) cell activation. Significance and Impact of Study: We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.